a

Food Science and Technology ISSN 0101-2061

DDOI: http://dx.doi.org/http://dx.doi.org/10.1590/1678-457X.0019

Lactose intolerance and cow’s milk protein allergy

Adriano Henrique do Nascimento RANGEL1, Danielle Cavalcanti SALES1, Stela Antas URBANO1*,
José Geraldo Bezerra GALVÃO JÚNIOR2, Júlio César de ANDRADE NETO1, Cláudia de Souza MACÊDO1

Abstract
Adverse reactions to food intake have very diverse etiology and symptomatology. Regarding milk, its food allergy is presented
as lactose intolerance, the sugar in milk, or allergy to milk protein. Despite having different symptomatology, confusions among
allergic conditions to dairy and its mediators are common. Milk protein allergy originates from protein components present in
milk, causing reactions to either the protein fractions in emulsion (caseins) or in whey (milk albumin). The allergic reaction is
type IV mediated by T lymphocytes. The allergic reaction produces severe cellular damage and it triggers physical, mental and
emotional symptomatology that may vary in time, intensity and severity. Lactose intolerance is originated by total or partial
absence of the enzyme that digests this disaccharide. Lactose intolerance can be primary or congenital and secondary; the former
being more rare and severe, the latter being more common. Lactase deficiency can be diagnosed by symptoms associated with
cramping and diarrhea. Thus, the objective of this study was to conduct a review of available literature on cow’s milk protein
allergy and lactose intolerance.
Keywords: cow’s milk; adverse reactions to food; immune response.
Practical Application: Know and differentiate lactose intolerance and allergy to cow’s milk protein.

1 Introduction
Successive changes in eating patterns have triggered serious
changes in the quality of life of human populations. The ease of
obtaining food associated with excess calories has made diseases
associated with overweight – hypercholesterolemia, dyslipidemia,
hypertension, and diabetes - more prevalent. Nutritional allergies
are also associated with the improvement of food standards,
with more reoccurring due to the global population’s access to
different types of food.
Due to its nutritional quality, milk – a product secreted by
the mammary glands of female mammals in postpartum – is an
important food source. Milk and milk product intake is associated
with better diet quality and has been associated with a reduced
risk of chronic diseases or conditions including hypertension,
cardiovascular disease, metabolic syndrome, Type 2 Diabetes
and osteoporosis (Bailey et al., 2013). However, there are allergies
related to milk consumption in humans, and this is the primary
reason for limiting or avoiding consumption of dairy foods.
With the increase in production and consumption comes
concern with the quality of the product reaching consumers,
especially when this product is related to various human health
problems such as cow’s milk protein allergy (CMPA), an adverse
immune response to dietary antigen in cow’s milk (Mc Williams
& Collins, 2014).
One of the main milk proteins is casein, which is the second
milk protein fraction to cause greater sensitivity in individuals.
This group of proteins constitutes about 80% of all milk proteins,
divided into four groups: s1 alpha, s2 alpha, beta and kappa.
Casein contains proteins that when digested are transformed
into opioid compounds known as β-casomorphins (BCM).
BCM bonds with A1 allele of β-casein, and it is believed that the
ingestion of this allele may cause allergies and other diseases to
the human body. On the other hand, A2 allele of β-casein has no
connections to such health problems. Some cow breeds have a
higher expression of A2 β-casein and produce less allergenic milk.
CMPA is the most common type of food allergy and usually
affects children, especially newborns. The overuse of cow’s milk
as a substitute for human milk has led to an increased incidence
of this disease (Carvalho-Junior, 2001). In CMPA, the child’s
body does not recognize one or more of the cows’ milk proteins
(casein, alpha-lactalbumin and beta-lactoglobulin), leading
to a reaction. In recent years, several companies have been
devoted to applying molecular or genetic markers to the bovine
milk agribusiness, since knowledge of genes is important for
bio‑economic characteristics in the production system, offering
benefits to agribusiness.
Overall, allergies and intolerances appear from the body’s
biochemical inability to digest, absorb and metabolize a specific
component. In the case of milk, lactose intolerance (LI) is the
body’s inability to digest lactose, due to the total or partial
absence of an enzyme specialized in this action called lactase.
On the other hand, allergy to cow’s milk protein (CMPA) is
characterized by immune reactions when the body comes in
contact with cow’s milk protein (Gasparin et al., 2010).

Received 22 Sept., 2015

Accepted 20 Nov., 2015
1
Universidade Federal do Rio Grande do Norte –UFRN, Campus Universitário Lagoa Nova, Natal, RN, Brasil
2
Instituto Federal de Educação, Ciência e Tecnologia do Rio Grande do Norte – IFRN, Campus Ipanguaçu, Ipanguaçu, RN, Brasil
*Corresponding author: stela_antas@yahoo.com.br

Food Sci. Technol, Campinas,        1

 Adverse reactions to cow’s milk
Intolerance to lactose and CMPA are often confused since
they are caused by the same food source, milk, and also because
they have some similar symptoms such as diarrhea and cramping.
Given this, differentiating between these two situations is essential,
as being intolerant makes it necessary to exclude or only eat low
amounts of foods containing lactose (depending on the degree
of the intolerance), and in cow’s milk allergy, the ingestion of
any milk protein or foods containing fractions of it must be
excluded to avoid triggering an allergic reaction.
Such facts have led researchers to study breeds and discover
which have higher genotypes and A1 and A2 allele frequencies.
Since then, those breeds presenting a greater amount of A1
allele began to produce A1 Milk is an allergenic milk that may
cause diseases to predisposed people. Thus, breeds with higher
amounts of A2 allele began to produce A2 milk, which does
not cause diseases and can be ingested by people with CMPA.
Thus, the objective of this study was to conduct a review
of available literature on cow’s milk protein allergy and lactose
intolerance.
2 Cow’s milk protein allergy (CMPA)
2.1 Overview
Milk is considered a staple food for children and an
essential supplement in the diet of adults, since it has a balanced
composition of nutrients with optimal digestibility, resulting in
a product with high biological value. However, its consumption,
in some cases, is associated with adverse reactions, such as cow’s
milk protein allergy (CMPA) (Bahna, 2002). Currently, the term
has been replaced by “adverse food reactions” – AFR (Reações
Adversas aos Alimentos – RAA) in order to reduce confusion
about definitions of each situation.
Adverse food reactions can be divided into two types: the
first being toxic adverse reactions, which depend more on the
substance ingested (e.g.: bacterial toxins present in contaminated
food) or pharmacological properties of certain substances present
in food (e.g.: caffeine in coffee, tyramine in matured cheeses)
(Sampson, 2004), and the second being non-toxic adverse
reactions, which depend on individual susceptibility and can
be classified as non-immune-mediated (food intolerance) or
immune-mediated (food hypersensitivity or food allergies).
The many causes of these adverse reactions may involve different
mechanisms, leading to the onset of a wide range of clinical
symptoms (Tumas & Cardoso, 2008).
Food allergy (FA) is a term used to describe adverse reactions
to food, dependent of immune mechanisms, mediated or not by
immunoglobulin E (IgE) and immunological cells. FAs mediated
by IgE are characterized by rapid installation, and those which
are non-mediated by IgE have later clinical manifestations (hours
or days), making diagnosis difficult (Eigenmann et al., 1998).
Usually cow’s milk, eggs, wheat and soy food allergies disappear
in childhood, unlike allergies to peanuts, tree nuts and seafood
that can be longer lasting and last the whole life (Eigenmann et al.,
1998). This disease affects the immune system, triggering action
mechanisms against the causative antigen, causing signs and
symptoms after food ingestion. In the case of cow’s milk allergy, the
2 Food Sci. Technol, Campinas,
causative agent is mainly found in dairy/milk and its derivatives.
The agents responsible for all of these reactions are cow’s milk
proteins, such as casein, β-lactoglobulin, α-lactalbumin, serum
albumin, and immunoglobulins (Gasparin et al., 2010).
Despite the body having the ability to digest milk proteins,
they are sometimes not recognized by the immune system, thereby
triggering the development/onset of allergies. This situation is
diagnosed as cow’s milk protein allergy, resulting in the need for
nutritional therapy (Benhamou et al., 2009; Luiz et al., 2005).
Cow’s milk protein allergy (CMPA) is the most common
food allergy in early childhood, affecting 2% to 5% of the child
population with less than three years of age (Huang & Kim, 2012).
It has a peak incidence at three months and is rarely observed
after six months of age. However, the incidence is significantly
less in infants who are exclusively breastfed, at a rate of about
0.5% to 1% (Helm, 2014). The fact that cow’s milk proteins
(CMP) constitute the first food antigens to be introduced into
the infant diet may partly explain this food allergy being the most
frequent and precocious (Vandenplas et al., 2007; Kneepkens
& Meijer, 2009; Orsi et al., 2009). The clinical presentation is
generally moderate in infants, which can be explained by CMP
concentration in breast milk (BM) being 100,000 times less than
the concentration found in infant formulas (Table 1).
Another factor associated with food allergies and especially
cow’s milk protein allergy (CMPA) is the early contact with this
food. At birth, the digestive system and the immune system of
newborns are still maturing; the enteric enzymatic system and
the immune system are not fully formed yet. The most ideal
food for babies is breast milk. Small amounts of proteins and
peptides consumed by the mother are passed through the milk
and therefore the baby will slowly be in contact with the food
they will consume in the future. This process is called tolerance
development (Dias et al., 2009).
In developed countries, cow’s milk protein allergy (CMPA)
affects between 2% and 7.5% of children, especially in the first
months of life. In a recent epidemiological study conducted in
pediatric gastroenterologists’ offices of the South and Southeast
regions of Brazil, 7.4% of 9,478 children were suspected of having
a food allergy, and cow’s milk protein allergy in 77% of cases.
In this study, the incidence and prevalence of CMPA suspicion
Table 1. Composition of the main proteins in breast milk and cow’s milk.
Protein Breast (mg/mL) Cow (mg/mL)
α-lactalbumin 2.2 1.2
α-s1-casein 0 11.6
α-s2-casein 0 3.0
β-casein 2.2 9.6
κ-casein 0.4 3.6
ϒ-casein 0 1.6
Immunoglobulins 0.8 0.6
Lactoferrin 1.4 0.3
β-lactoglobulin 0 3.0
Lysozyme 0.5 Traces
Serum albumin 0.4 0.4
Other 0.8 0.6
      
 Rangel et al.
calculated by the diagnostic reported by surveyed physicians
were 2.2% and 5.7%, respectively (Luiz et al., 2005). Furthermore,
the reported prevalence of CMPA varies dramatically between
studies, which may be attributable to different methods being
used for diagnosis or differences in the ages of the studied
populations (Venter & Arshad, 2011).
Several predisposing factors have been proposed, but so
far none have been confirmed. There seems to be a genetic
predisposition, as about two thirds of children with CMPA have
a history of atopy in first degree relatives. Also, environmental
factors such as neonatal antecedents that alter the formation of
intestinal flora, as well as prematurity, antibiotic therapy early
in life, or early and sporadic contact with CMP in utero through
breast milk or through occasional formula administration to infants
seem to cause CMPA predisposition. Exclusive breastfeeding for
four to six months appears to be a protective factor, for not only
CMPA but also other food allergies (Vandenplas et al., 2007;
Kneepkens & Meijer, 2009).
The pathophysiological mechanism by which food allergies
develop involves processes of fundamental importance such as the
permeability of the gastrointestinal tract barrier and individual
genetic predisposition, in addition to antigens (protein of molecular
weight between 10 and 70 kDa). The physiological immaturity
of the digestive system inherent in the first two years of life and
the immature immune system at this age are important factors
in order to establish the development of CMPA in childhood.
Milk from other mammals (goats and sheep) are similarly
antigenic to cow’s milk, and so there is no advantage in their use as
preventive to cow’s milk protein allergy. It is noteworthy that 90%
of children allergic to cow’s milk protein also present an allergic
reaction to goat and sheep milk, and that the association with a
food allergy to beef is extremely rare (Eigenmann et al., 1998).
2.2 Signs and symptoms
Most children with CMPA develop symptoms before
the first month of age, often during the first week of dairy
introduction and it can affect several organs of the body, causing
more than one symptom, or even symptoms in more than one
organ. Approximately 50% to 70% of subjects have cutaneous
symptoms, 50% to 60% gastrointestinal symptoms and 20% to
30% respiratory symptoms (North American Society for Pediatric
Gastroenterology Hepatology and Nutrition, 2010).
The characteristic signs and symptoms result from immediate
gastrointestinal hypersensitivity after allergen ingestion and
can cause nausea, vomiting, abdominal pain and diarrhea,
leading to weight gain deficit and malnutrition, also due to
intestinal malabsorption or energy loss of food eliminated by
vomiting and regurgitation. Some may present a rash, pruritus,
angioedema, bronchospasm, oral allergy, eosinophilic esophagitis,
gastroesophageal reflux, cramps, eosinophilic gastroenteropathy,
enteropathy, enterocolitis, allergic colitis, chronic constipation,
and skin and respiratory disorders (Vonk et al., 2003).
Morais & Fagundes (2003) report that it is common for
children in their first year of life to have diseases like CMPA and
gastroesophageal reflux disease (GERD), often even interconnected.
Food Sci. Technol, Campinas,        3
Symptoms such as low birth weight and malnutrition, vomiting,
hematemesis, constipation with pain, chronic diarrhea with
malabsorption and rectal bleeding can result from GERD
secondary to CMPA gastritis, although not being a very common
expression of this pathology. They observed two cases in which
children stopped receiving breast milk in the first three months
of life, with symptomatic condition starting right away. After
a final diagnosis, they were both diagnosed with hemorrhagic
gastritis from cow’s milk protein allergy.
2.3 Milk proteins
Milk provides high quality and proteins in significant
amounts, providing an average of 3.5 g to 3 g of protein per
100 g of milk. After blood proteins, milk proteins are probably
the most well characterized from the physico-chemical and
genetic point of view. They have the advantage of being proteins
from an animal source, being cheaper and possessing high
biological value. They are used as ingredients in various food
products, and individually they can display several beneficial
functions to the organism, such as increased calcium absorption
and immune functions, lowering blood pressure and the risk
of cancer (Host, 2002).
Milk proteins are divided into multiple classes of polypeptide
chains, the main one being: casein, beta-lactoglobulin and
alpha‑lactalbumin. According to Cortez  et  al. (2007), milk
contains more than 20 protein components provided with
different degrees of antigenic activity, and in several studies
subjects allergic to milk showed that their sensitivity to each
protein fraction follows frequencies shown in Table 2.
The casein group represents around 75% to 85% of milk
proteins and nearly all of them are associated with calcium and
phosphorus in micelles of 20 to 300 µm in diameter that reflect
light, creating the characteristic white color of milk. Because
of their excellent nutritional value, caseins are used by many
authors as the reference protein for assessing food protein quality.
Although the major compounds of CMPA are supposedly found
in casein fractions of β-lactoglobulin (β-lg) and α-lactalbumin
(α-la), all milk proteins are potential allergens, including those
present in smaller concentrations (Carvalho-Junior, 2001).
Some authors have shown that most of the 92 CMPA patients
evaluated were susceptible to several proteins. Of those, only
26% were mono-sensitive; 17, 22, 20 and 15% of patients were
sensitive to two, three, four and five allergens, respectively.
The  main proteins indicated in this study as having higher
allergen potential in weight were casein, β-lactalbumin and
α-lactalbumin, since 65, 61 and 51% of patients were specifically
Table 2. Sensitization percentage of protein fractions.
Protein fraction % of sensitive individuals
Beta-lactoglobulin 66-82
Casein 43-60
Alpha-lactalbumin 41-53
Bovine Serum Globulin 27
Bovine Serum Albumin 18
Source: Cortez et al. (2007).
 Adverse reactions to cow’s milk
sensitized by the aforementioned proteins, respectively. Some
proteins present in small concentrations, such as bovine serum
albumin, immunoglobulins and lactoferrin, also appear to
have great importance in the process, since 43, 36 and 35%
of the patients were sensitive to these proteins, respectively
(Cocco et al., 2007).
Casein acts as a potent allergen in CMPA where each
different fraction (S1-, S2, β- and κ-casein) can induce specific
IgE responses. The largest phosphorylation sites appear to
be a major allergen epitope in caseins and changes in these
regions could affect the allergenicity of these (Naspitz  et  al.,
2004). According to a study by Reis & Vaz (2004), caseins were
predominantly allergenic and immunogenic in patients with
IgE-mediated CMPA compared to whey proteins.
Caseins are divided into four groups: s1 alpha (30%-46%
of caseins), s2 alpha (8%-11%), beta (25%-35%) and kappa
(8%-15%) and are encoded by genes present on the bovine
chromosome 6 (Vercesi, 2011). In the 1970s, the amino acid
sequence of the four caseins was determined. In this same decade,
the genetic variants from each of them started to be discovered,
differing from each other by an amino acid or a group of them.
All caseins contain high amounts of non-polar amino acids, and
likely reduced solubility in water, but the relative abundance
of phosphate groups, the lack of sulfur, and the presence of a
carbohydrate moiety make them very polar (Ordóñez, 2005).
Ordóñez (2005) also explains that caseins are rich in
proline. The α-s1 contains 17 residues, the α-s2 10, the β 35 and
the κ 20 residues. The high number of proline residues makes
the structure degree in these proteins smaller than in others.
The least organized is beta-casein, where 70% of its residues do
not form a secondary structure.
Beta-casein is the second most abundant protein in milk,
in addition to being crucial for casein micellar structure. It has
a polymorphic condition/state and is composed of 209 amino
acids, which are divided into 13 variants: A1, A2, A3, B, C,
D, E, F, H1, H2, I and G. Variants A1 and A2 are described as
the most common beta-casein allelic variants in dairy cows
(Farrell et al., 2004; Vercesi, 2011). Due to its polymorphic nature
and association with fat and milk protein, they have attracted
several efforts in evaluating their locus as a main peculiarity for
industry (Kucerova et al., 2006).
A1 and A2 variants are differentiated by the change of one
nucleotide in the position 67 of the chain (A1 histidine and A2
proline). Studies have indicated that initially the entire bovine
population contained only the A2 allele, and A1 allele was created
from a mutation (Vercesi, 2001). Due to the subtle differences
in their structures, these beta-casein variants are digested
differently. For A2 beta-casein, the enzymatic hydrolysis does
not occur or occurs at very low rates, producing the peptide
beta-casomorphin-9 (BCM-9). In contrast, the digestion of A1
beta-casein can produce the exogenous opioid peptide called
beta-casomorphin-7 (BCM-7) (European Food Safety Authority,
2009; Sodhi et al., 2012).
It is believed that BCM-7 is a major cause for health related
problems in humans (Trompette et al., 2003), which is why the
consumption of A1 Milk has been associated with a large increase
4 Food Sci. Technol, Campinas,
in diseases such as diabetes mellitus type I (Thorsdottir et al.,
2000), coronary disease (McLachlan, 2001), arteriosclerose
(Tailford et al., 2003), sudden infant death syndrome (Sun et al.,
2003), schizophrenia and autism (Woodford, 2008), as well as
allergies. On the other hand, Kaminski et al. (2007) claim that
the A2 allele has no connection with such health problems.
According to Vercesi (2001), CSN2 is encoded by genes present
in the bovine chromosome 6.
2.4 Dairy breeds and polymorphisms in the β-casein gene
A study involving Norwegian Red dairy cows (Nilsen et al.,
2009) found favorable genetic association of the A2 allele with
higher milk and protein production. A similar result was obtained
by Olenski  et  al. (2010), who found a positive association
between the A2 allele and the genetic merit for milk and protein
production, and a negative association between this gene and
the genetic value for the fat percentage in Dutch cows in Poland.
Therefore, on top of adding value to human health, A2 allele
beta-casein may be associated with higher production of milk
and protein in cattle. New Zealand currently has dairy farms
producing only milk with A2 protein (called A2 milk), due to
assumptions that this variant is not harmful to human health,
as opposed to variant A1 (Vercesi, 2001).
In Brazil, about 80% of the milk is produced by crossbred
animals from mating taurine (predominantly Dutch) with zebu
(predominantly Gyr) breeds. Of the total semen produced
and marketed in Brazil for dairy production, the Gyr breed is
responsible for about 48%. This fact led researchers to study all
breeds and discover which produced larger amounts of A1 and
A2 milk (Garcia, 2009).
A genetic study conducted in the University of São Paulo in
São Carlos demonstrated that zebu breeds are almost entirely still
producing A2 milk (close to 100%) and have not been affected by
this genetic mutation. In addition to the known characteristics
of rusticity and external parasite resistance, there is now another
advantage; Gyr milk is non-allergenic (Garcia, 2009).
In a study conducted by Lima (2014) with flocks of Gyr
and Guzerá, a high frequency of A2 allele and A2A2 genotype
was observed in β-casein genes in the evaluated cattle; they also
claim that the selection of Zebu breeds with this high frequency
allele is emerging as a viable alternative for the production of
non-allergenic milk.
In taurine breeds (European), only the Guernsey breed, a
once well-established dairy breed in Brazil that unfortunately
became extinct due to several factors but now has increasing
levels worldwide, exclusively produces A2 milk; the Jersey breed
is in second place with 75% of A2 milk and 25% of A1 allergenic
milk; and the Holstein breed, with 50% A1 milk and 50% A2
milk (Lima, 2014).
3 Lactose intolerance
3.1 Overview
Lactose intolerance is intolerance to the most common
carbohydrate in milk affecting all age groups (Matthews et al.,
2005). It could be described as an intestinal mucosa disorder that
      
 Rangel et al.

incapacitates the digestion of lactose due to the deficiency of an Table 3. Primary adult hypolactasia prevalence in different populations.
enzyme called lactase (Heyman, 2006; Qiao et al., 2011). This is Country Prevalence (%) Method1
a generic term that refers to the varied clinical manifestations Germany 14.8 BH
caused by adverse reactions triggered by food. Austria 20.1 BH
This pathology is characterized by a set of clinical symptoms Brazil (white) 57.0 G
accompanying lactose maldigestion, representing 2% to 8% Brazil (Terenas Indians) 89.3 BH
of its solid portion. This compound belongs to the group of Brazil (Japanese) 100.0 G
carbohydrates included in the group of sugars classified as a Brazil (mulattos) 57.0 G
disaccharide. The “sugar in milk,” a popular name for lactose, Brazil (Negroes) 80.0 G
has its molecule formed by two simple sugars, which are glucose China 87.3 G
and galactose joined by a glycosidic linkage which facilitates the Estonia (Finnish-background) 24.8 G
absorption of this main milk glycide and is used as an energy France 23.4 BH
source by the body (Morais & Fagundes, 2003). Hungary 37.0 G
India (North) 67.5 G
Lactose is present in several types of milk, and all mammals,
India (South) 86.8 G
including humans, when born under normal conditions are able
Italy 51.0 BH
to digest this sugar. However, about 75% of the world population
suffers from lactose intolerance, where the incidence in adults Japan (adults) 89.0 BH
is less than 20% (Swagerty et al., 2002). Jordan (Bedouin) 24.0 BH
Jordan (West) and Palestine 75.0 BH
According to Jellema et al. (2010), Epidemiological studies Russia (Northeast) 35.6 G
show that the populations which depended on livestock in their Siberia (Khants) 94.0 G/T
early days much more than agriculture, and those that were major Somalis 76.0 BH
consumers of milk and dairy products in general, had a lower Sudan (Béja tribe. farmers) 16.8 BH
prevalence of lactose intolerance than those who depended more Sudan (Nilotis tribe. farmers) 74.5 BH
on agriculture to survive, as presented in Table 3. Sweden (Caucasian children) 10.0 G
Ethnic groups such as blacks, Hispanics and Asians are more Sweden (non-Caucasian children) 66.0 G
likely to develop this intolerance (Swallow et al., 2001). Studies Sweden (Caucasian elderly) 5.0 G
conducted in Brazil using lactose overload (50 g/d) in several Tuareg 12.7 BH
individuals have shown that 70% of them presented different Turkey 71.3 BH
degrees of lactose intolerance (Semrad & Powell, 2008). 1
Breath hydrogen test (BH). Genetic (G) and Glycemia/Tolerance (G/T).
Source: Jellema et al. (2010).
Moreover, some studies have shown that extreme age groups,
infants and the elderly are also often affected, rarely being lactose
intolerant from birth (Semrad & Powell, 2008). Most newborns into the bloodstream for absorption. Galactose is enzymatically
have lactase when they are born and can digest lactose as infants. converted into glucose, which is the main metabolic fuel of
If an infection or food allergy affects the small intestine, the many tissues. The lactase activity is high during the neonatal
child can develop lactose intolerance, causing a reduction in period, but it declines during weaning (Matthews et al., 2005).
lactase. Usually this damage is temporary, but it can take weeks
or even months until the child can tolerate milk and dairy When lactose reaches the intestinal lumen, it must be
products again. Children naturally start to produce less lactase hydrolyzed into monosaccharides by lactase, which is an
at ages 3-6 than in the first two years of life. In some children endo‑enzyme present in the brush border membrane of the
the production continues to decline, or may cease altogether. intestinal mucosa (epithelial cells of the intestinal lining)
Symptoms of lactose intolerance often appear in adolescence (Heyman, 2006). Intestinal disaccharides are synthesized by
or early adulthood (Swallow et al., 2001). polysomes of the rough endoplasmic reticulum of enterocytes.
They migrate to the Golgi apparatus where glycosylation is
completed. Then they are transported in Golgi vesicles to the top
3.2 Lactose
of the membrane of mature enterocytes of small intestine villi,
Lactose, commonly known as milk sugar, is a disaccharide where they are attached and become more vulnerable to attacks
composed of glucose and galactose formed by the mammary than other disaccharides. The gene responsible for the lactase
glands of mammals through glucose to supply the carbohydrate synthesis is located on chromosome 2 (where mutations may occur
component during lactation, and is the same found in cow’s interfering with the disaccharide tolerance) (Tevês et al., 2001).
milk, human breast milk and all other mammals (Lomer et al.,
The products of the lactase enzyme on lactose (glucose and
2008). Therefore, there is no possibility of an “allergy to lactose”
galactose) are absorbed by the mucosa of the small intestine.
happening from the lack of specificity or for it being a non-protein
A small amount of carbohydrates may not be digested by enzymes
component. Its concentration in milk varies depending on the
and reach the colon intact, thereby suffering fermentation by local
type of mammal; in cow’s milk the average is 7%.
bacterial flora, and with the production of short chain fatty acids
This disaccharide is hydrolyzed by the intestinal enzyme (butyric acid, propionic acid, acetic acid), and gases (CO2 and H2).
β-D‑galactosidase or lactase, releasing monosaccharide components The products of carbohydrate bacterial fermentation are absorbed

Food Sci. Technol, Campinas,        5

 Adverse reactions to cow’s milk
in the colon and the calories are used up, thus contributing to
the maintenance of the energy balance. This process is known
as colonic rescue of carbohydrates (Tevês et al., 2001).
Under normal conditions, lactase is present in distal cells
of the intestinal mucosa villi to perform lactose digestion.
In deficiencies when disaccharidase activity is low, the events in
the colon are accentuated by a higher rescuing of products that
could have toxic effects to the organism and increased production
of short chain fatty acid (SCFA), H2 and CO2, which play an
important role in clinical manifestations (rashes, flatulence,
bloating and abdominal pain), since they cause intestinal
distension. The undigested lactose increases the osmotic load in
the digestive tract, which adds to the clinical symptoms of lactose
intolerance. The lactic acid produced by the microorganisms is
osmotically active and pull water as well as undigested lactose,
into the intestines resulting in diarrhea (Matthews et al., 2005).
The presence of osmotically higher content than intestinal
lumen mucosal cells osmolarity determines the passage of
water and, to a lesser extent of electrolytes of these cells to the
enteral light in order to equalize osmotic pressure. Thus, large
amounts of carbohydrates, whether digested or not, retain
large amounts of water when they are not absorbed into the
intestinal lumen in attempting isotonicity. When the amount
of electrolytes lost is lower than the water, evacuations tend to
be liquid (Swagerty et al., 2002).
The absorption of glucose and galactose is done at different
speeds. The determining factor for maximum speed of lactose
absorption depends on the amount of lactase present in the
intestinal mucosa. Monosaccharides go through the mucosa and
are actively transported into the bloodstream. Both glucose and
galactose depend on sodium to be transported. When they are
in the bloodstream, they travel through the portal vein to the
liver where they are metabolized (Guerra, 2011).
Although lactase levels are normal in infancy, in adulthood
these individuals start to present low levels of this enzyme.
This decrease of quantity and the intestinal lactase activity is
determined by genetic factors. However, it also is influenced
by environmental factors such as the presence of malnutrition,
parasites, intestinal infections and alcoholism. Moreover, in some
cases it may represent an adaptive response to the decrease of
dairy product intake (Guerra, 2011).
3.3 Signs and Symptoms of Lactose Intolerance
Signs and symptoms of lactose intolerance are similar to
any other specific enzyme deficiency. They include abdominal
pain, bloating in the abdomen, flatulence, diarrhea, intestinal
noises, and particularly in the young, vomiting. Abdominal
pain may be crampy and is often located in the periumbilical
region or lower quadrant. The intestinal noises may be heard
during the physical examination and by the patient. The stools
are usually bulky, frothy and watery. An important feature is that
these individuals usually do not lose weight, even with chronic
diarrhea mentioned above. In some cases, gastrointestinal motility
is reduced and the subjects may have constipation, possibly as
a result of methane production (Guerra, 2011).
6 Food Sci. Technol, Campinas,
Even when only lactose absorption is directly damaged by
lactase deficiency, the resulting diarrhea can be intense enough
to remove other nutrients before they can be absorbed and may
cause malnutrition, especially in children. Lactose intolerance is
also responsible for many systemic symptoms, such as headaches
and dizziness, loss of concentration, short term memory difficulty,
muscle and joint pain, severe tiredness, various allergies, cardiac
arrhythmia, oral ulcers, sore throat and increased frequency of
urination. In the presence of systemic symptoms, it is necessary
to evaluate if in fact they result from lactose intolerance, whether
they are coincident symptoms or result from allergy to cow’s
milk protein (which affects up to 20% of patients with symptoms
suggestive of lactose intolerance) (Guerra, 2011).
There is a wide variability of symptoms among patients with
lactose intolerance. The factors responsible for this variability
include the osmolality and food fat content in which the
sugar is ingested, stomach emptying, sensitivity to abdominal
distension produced by the osmotic load of the lactose which
is not hydrolyzed in the upper small intestine, intestinal transit
and the colon’s response to the carbohydrate load. Generally,
foods with a high fat content and osmolality decrease gastric
emptying and reduce the severity of symptoms induced by
lactose (Jellema et al., 2010).
Depending on the intensity of lactose intolerance, net
losses from diarrhea can be very large and result in major loss
of electrolytes, particularly sodium and potassium, as well as
dehydration. Hyponatremia may be aggravated by inadequate
replacement at the expense of poor liquids or being exempt
of sodium. However, in osmotic diarrhea, the fluid losses are
greater than sodium, as other molecules draw water into the
intestinal lumen. Thus, hypernatremia occurs which increases
when the replacement is also incorrect, providing excess sodium
with respect to water. Hypernatremic dehydration is found in
children, especially under 2 years of age and may endanger the
life of the patient when treatment is not done with balanced
solutions (Jellema et al., 2010).
The amount of lactose ingested in order for it to trigger
symptoms vary for each individual depending on the dose of
lactose ingested, the degree of lactase deficiency, and type of food
with which the lactose has been consumed, and the severity of
the symptoms depends on the amount of lactose that the person
can tolerate (Tumas & Cardoso, 2008).
4 Differences between the pathologies
Clinical manifestations of milk protein allergy related to the
digestive tract are very similar to those of lactose intolerance,
which can easily lead to misdiagnosis. However, CMPA can cause
skin lesions (atopic eczema) and also respiratory symptoms,
which does not occur in lactose intolerance. Lactose intolerance,
in turn, is purely a matter of digestion and absorption, with no
immunologic mechanism involved in the pathophysiology, and it
affects adults more frequently than children. Its evolution can be
transient or definitive (Tumas & Cardoso, 2008). The difference
of the characteristics between these two pathologies is described
in Table 4.
      
 Rangel et al.

Table 4. Differentiating characteristics between lactose intolerance and cow’s milk protein allergy.
Lactose intolerance Cow’s milk protein allergy
Difficulty in lactose digestion and
Definition Allergic reaction to one or more cows’ milk proteins.
absorption.
More common in adults; there is a
Age of onset natural tendency to develop LI in the More common in children, especially infants.
ageing process.
Diarrhea, cramping, abdominal
Vomiting, cramping, abdominal pain, constipation, bloody stools, growth deficiency,
Clinical distension, nausea, bloatedness. May
gastroesophageal reflux, dermatitis, asthma, rhinitis. May appear minutes or days after the
condition appear minutes or hours after ingesting
ingestion of milk or dairy.
food with lactose.
It can evolve as temporary or
Prognosis permanent. Most people with LI tolerate 50% of cases evolve into being cured by 12 months of age, and 90% by 3 years of age.
small amounts of lactose.
Source: Tumas & Cardoso (2008).

Even with so much information available, many people
still have difficulties in identifying the differences between
lactose intolerance and allergy to milk protein. These doubts do
not occur only with patients; many health professionals have
trouble with concluding the diagnosis, generating nutritional
complications in patients.
5 Conclusion
CMPA is totally linked to immune responses, since it is
the defense to a protein not recognized by the body; lactose
intolerance is a metabolic disorder caused by an absence of lactase,
and thus has the characteristic of not being able to absorb the
sugar present in cow’s milk. These conditions are similar in some
points, such as in the symptoms, as both have gastrointestinal
reactions. However, with the allergy there can be no intake of
the milk protein, as its consumption is only recommended after
treatment. In LI, deprivation occurs also from milk, but some
people can consume some types of dairy products, as long as
lactose has been previously hydrolyzed.
However, independent of the condition, there can be no
diagnostic errors as there will be implications on the nutritional,
physical and psychological state of the patient. Because of this,
it is essential that professionals know how to recognize the most
appropriate way possible to not submit the patient to greater
losses exacerbating the responses to the aggressor. So professional
nutritionists need to analyze and adapt to the nutrient intake,
optimizing the availability of macro and micronutrients necessary
for the maintenance and good health.
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